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Hepatitis C breakthrough could save chimpanzees from medical research

With the discovery of new rodent viruses closely related to the human hepatitis C virus, scientists hope that they will be able to develop a new animal model to study the devastating disease, instead of having to use chimpanzees.

With the discovery of a new virus in wild mice that is closely related to the human hepatitis C virus, it may soon be possible to phase out the use of chimpanzees like this ape seen in a lab at Ohio State University in 1999. (TERRY GILLIAM / The Associated Press file photo)

The discovery of a virus in wild mice that is similar to the human hepatitis C virus means it is possible that lab mice, like these animals seen at a medical school in Chongqing Municipality, China, in 2008, could be used to replace chimpanzees in hepatitis C research.
(China Photos / GETTY IMAGES)

The long-suffering laboratory chimpanzee may have found an unexpected saviour in the common deer mouse, thanks to the discovery of new rodent viruses scientists hope could be a game changer for hepatitis C research.

Policy-makers now widely agree that chimpanzees, our closest relative in the animal kingdom, should no longer be used for medical research if there are alternative animal models. The great apes have now been phased out of laboratories everywhere except for Gabon and the United States — and in the latter country, the National Institutes of Health will soon announce the fate of its 360 research chimpanzees, most of which were recommended for retirement in January.

But when it comes to hepatitis C, which chronically infects about 170 million people worldwide and is the number one reason for liver transplants, chimpanzees are the only animals that work for research. They are the one species, other than humans, that can be infected with human hepatitis C.

There is no prophylactic vaccine for the virus and research toward finding one has heavily relied on experiments using chimpanzees. Between 2001 and 2010, 40 per cent of chimpanzee projects sponsored by the NIH were for hepatitis research.

In 2010, the NIH also asked the U.S. Institute of Medicine to form an expert panel to investigate whether chimpanzees were still necessary for biomedical research. The panel said that chimpanzees raise additional ethical concerns that don’t exist for other research animals because of their close genetic similarity to humans; therefore, their use demands greater justification. The panel agreed that most chimpanzee projects at the time should be shut down, but it could not reach a decision on the future of chimpanzees in hepatitis C vaccine studies.

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But a recent study published in the journal mBio has unveiled a potential substitute for the lab chimp: wild mice. Led by Columbia University researchers, the study describes the discovery of several hepatitis C-related viruses in rodents. The hope is that these viruses, if found to behave similarly to hepatitis C, could provide a new avenue for studying the disease.

“I think people for decades were waiting for something like this,” said study lead author Dr. Amit Kapoor, a researcher with Columbia University’s Center for Infection and Immunity. “Finding a virus in rodents, which would be an ideal candidate to develop an animal model system, is really a breakthrough.”

When it comes to zoonotic diseases (diseases that have crossed over into humans from animals), studying the animal origin of the virus can be hugely valuable. Simian immunodeficiency virus, for example, is the chimpanzee virus that gave rise to HIV and scientists have studied it closely to unlock information about HIV in humans and potential vaccines.

But the ancient animal reservoir for hepatitis C remains a mystery. Several attempts to find a similar virus in animals have been unsuccessful — until about two years ago.

That’s when Kapoor and his centre’s director, Dr. Ian Lipkin, made a startling discovery while studying a respiratory outbreak in domestic dogs. They found a brand new virus — and it was related to human hepatitis C.

This “was a big deal for the field,” Kapoor said — the hunt for hepatitis C-related viruses had mostly been focused on primates. Kapoor decided to cast a wider net and started testing various four-legged animals, including 103 horses; about 35 per cent of them had evidence of a hepatitis C-like virus.

But dogs and horses are no good for laboratory research; they are large, cumbersome and carry their own ethical concerns.

Mice are vastly more ideal: small, inexpensive, easily genetically manipulated and less prone to generating controversy. So, Kapoor thought: why not look for the viruses in mice?

After combing through more than 400 frozen rodent carcasses and blood samples, Kapoor and his co-researchers found several new rodent viruses, five of which were genetic “cousins” to human hepatitis C.

Lipkin, the study’s senior author, is hopeful this study will result in a workable mouse model, but warns it is too soon to know for sure. He and Kapoor will now try to infect different mice with the rodent viruses. If this fails to cause liver inflammation, as hepatitis C does in humans, then “it really isn’t a relevant model,” Lipkin said.

For Lipkin, finding a laboratory alternative for chimpanzees was a “major factor” in deciding to pursue this research.

“I never felt good about working with chimpanzees for anything,” he said. “We have a cultural acceptance of working with certain animals above others, but chimpanzees are really beyond the pale.”

There are certainly limitations when it comes to using mice, Ploss said, “but we are in a somewhat desperate situation in that we don’t have anything else.”

With the phasing out of laboratory chimpanzees, hepatitis C vaccine research has been the one holdout, but this study may change that, said Jeffrey Kahn, a bioethicist with Johns Hopkins University and chair of the expert panel that investigated the issue for the NIH.

“If there is indeed a good animal model other than chimpanzees, that would pretty much take the only remaining justifiable use of chimpanzees off the table,” he said.

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